Asthma and other respiratory diseases have long been treated by the inhalation of appropriate medicament. For many years the two most widely used and convenient choices of treatment have been the inhalation of medicament from a drug solution or suspension in a metered dose pressurized inhaler (MDI), or inhalation of powdered drug generally admixed with an excipient, from a dry powder inhaler (DPI). With growing concern being voiced over the strong link between depletion of the earth's ozone layer and chlorofluorocarbon emissions, the use of these materials in pressurized inhalers is being questioned and interest in DPI systems has been stimulated.
Known single and multiple dose dry powder devices use either individual pre-measured doses, such as capsules containing medicament which is inserted into the device prior to use, or incorporate a bulk powder reservoir from which successive quantities of medicament are transferred to a dispensing chamber. While it is desirable to utilize the action of a patient's breathing both to aerosolize powdered drug in the device and inhale the powder, thereby overcoming the coordination problems necessary to synchronize inspiration with means for medicament release, the efficiency of aerosolizing the particles of powder is dependent upon the patient's inspiratory effort and in some cases a patient having breathing problems, e.g., during an asthmatic attack, may have insufficient inspiratory effort to aerosolize and inhale the required dose of medicament at a time when the patient has the greatest need for drug.
Agglomeration is caused by particles of medicament adhering together in a semi-rigid mass, and requires an increased inspiratory effort by the patient to break up and entrain drug particles into the air stream. If the patient is unable to provide sufficient inspiratory effort the extent of drug penetration into the lower airways of the lung will be reduced. Larger agglomerated drug particles (approximately 10 .mu.m or greater) which result from inefficient aerosolization are not stably entrained into the patient's air stream and prematurely deposit in the mouth/throat region which may lead to unwanted systemic side effects, especially when potent drugs are administered.
Some inhalation devices have attempted to solve the problems attributable to agglomeration and medicament release, for example, U.S. Pat. Nos. 3,948,264, 3,971,377 and 4,147,166 disclose inhalers for dispensing medicament in the form of a dry powder contained in a rupturable capsule. After breaching the capsule the patient is required to externally manipulate means for operating a power source to provide the input of energy, necessary to release medicament from the capsule, while simultaneously inhaling through the device.
U.S. Pat. No. 3,948,264 discloses the use of a battery powered solenoid buzzer to vibrate the capsule effecting medicament release.
U.S. Pat. No. 3,971,377 discloses the use of a propeller to generate an airflow effecting medicament release. The power source comprises an electric motor, battery and external switch combination or a threaded plunger arrangement.
U.S. Pat. No. 4,147,166 discloses the use of an impeller to generate sufficient air turbulence to effect medicament release. The power source comprises a battery driven motor, a compressed gas power turbine or a hand power driven differential gear.
These devices are unsatisfactory as they permit deagglomeration/aerosolization to take place for an uncontrolled period of time prior to inspiration, additionally, the patient may forget to activate the device before inhalation. Thus, the size and effectiveness of the dose received by the patient's respiratory system may vary between individual patients and/or between individual occasions of use.
British Patent Specification Nos. 898649 and 1479283 disclose dry powder inhalers comprising either a manually squeezed bellows or bulb to generate greater than atmospheric pressure in an air reservoir. Inspiration by the patient operates a valve mechanism which discharges the compressed air into a chamber containing a dry powder capsule and hence into the patient's respiratory system. However, the aforementioned devices remain patient dependent even though the energy used to aerosolize and deagglomerate the powder is not supplied by the patient's inspiratory effort. The degree of pressure exerted upon the bulb or bellows will affect the energy supplied by the compressed air which in turn will effect the nature of the dose of powdered drug inhaled. For example, old, arthritic or very young patients may exert considerably less pressure than a more able individual. Similarly those individuals afflicted with an asthma attack find the devices cumbersome and/or complicated at a time when they are under severe stress. Furthermore, in each case the patient must remember to operate the squeezy bulb or bellows prior to inhaling, and must continue to exert pressure on these means during inhalation.